Biology Reference
In-Depth Information
Studies of erythropoiesis and the discovery and
cloning of recombinant human erythropoietin
MaryAnn Foote
Amgen Inc., One Amgen Center Drive, M/S 17-2-A, Thousand Oaks, California 91320, USA
Introduction
Patients who are anemic because of chronic kidney disease, cancer, arthritis,
or chemotherapy or radiation therapy often report fatigue [1-6]. Before the
introduction of recombinant human erythropoietin (rHuEPO), anemia and its
sequelae fatigue were treated with red blood cell transfusion, androgen stimu-
lation of red blood cell production, and/or iron supplementation, among other
treatments [7]. While effective in increasing red blood cell counts, both trans-
fusions and androgen therapy have inherent risks [8]. Transfusions of red
blood cells can be complicated by blood-borne pathogens, iron overload,
immunologic consequences, and lack of or delayed hemoglobin response.
Transfusions often improve but do not correct anemia and usually must be
given frequently, and androgen therapy can cause viralization or abnormal
liver function. rHuEPO is an ideal therapy because it mimics the action of the
endogenous hormone by stimulating the production of red blood cells. Patients
with chronic kidney disease are unable to produce adequate amounts of
endogenous erythropoietin (EPO) to stimulate red blood cell production.
Patients with cancer often have damaged bone marrow, with or without the
insult of chemotherapy, that does not completely respond to the endogenous
hormone.
The cloning of the human
EPO
gene by Fu Kuen Lin and colleagues was a
difficult and frustrating endeavor. This milestone and the subsequent creation
and production of rHuEPO as a therapeutic option was a breakthrough that has
enabled physicians to ameliorate anemia and its sequelae. Patients treated with
rHuEPO report a return to more normal lives. rHuEPO is the standard of care
for treatment of anemia in patients with chronic kidney failure or receiving
chemotherapy, and in other disease settings.
This chapter is a literature review of the history of the early work in ery-
thropoiesis and the discovery and cloning of EPO. Other chapters discuss its
commercial production and the clinical uses of rHuEPO.
